The uptake of a lysosomal enzyme, alpha-L-iduronidase, into fibroblasts from patients with the Hurler Syndrome, appears mediated by interaction of a component of the enzyme ("recognition marker") with a receptor on the cell surface. The structure of that marker, and its alteration in the genetic mucolipidoses will be determined; identification and purification of the receptor will be initiated. An antibody to alpha-L-iduronidase will be used to search for cross-reacting mutant proteins in cells of Hurler and Scheie patients; to trace the path of this enzyme from its site of synthesis to its eventual location in lysosomes; and to examine cell surfaces, by immunofluorescence, for bound enzyme. Similar studies will be initiated for iduronate sulfatase, the enzyme deficient in the Hunter Syndrome, to determine if each lysosomal enzyme has a unique receptor.